Blanco was born in Tlatilco, but grew up in Tepito, where he learned to love playing football in the local fields. Growing up in a rough environment, Blanco developed a style of play based on creativity. Ángel González a scout for Club América discovered him as he won the Torneo Benito Juárez as a part of the Distrito Federal selection team, and brought him to Club América's development program.

Having played most of his career in Club América, with 333 appearances and 135 goals, Cuauhtémoc has become an idol to the club's supporters and an important figure in the history of the team.

Blanco made his debut in the México Primera División in 1992 at age 19 with Club América. He won his first Golden Boot with 16 goals in the Winter 1998 season for Las Aguilas.

In May 2005, Blanco won his first club championship as a player, leading Club América to its tenth league title, when Club América defeated U.A.G. by an aggregate score of 7–4 (1–1, 6–3). In the next three consecutive years between 2005 to 2007, he was awarded the MVP.

He scored his last goal is this club during the championship final against Pachuca in 2007. After that game he moved to Chicago and played the next two seasons for Chicago Fire.

In the year 2000, after winning the Golden Shoe in the Confederations Cup 1999, Blanco was loaned to Real Valladolid for the 2000–01 campaign. On October of that year in an international WCQ match against Trinidad and Tobago, he received a strong kick from an opposing defender, breaking his leg and leaving him out of the fields for the next six months.

After the peak of his career was stopped by an injury, he continued in the club for another season (2001–02), in which he struggled with homesickness and regaining his form; after scoring great goals in Spain, including a great free-kick against Real Madrid C.F. at the Santiago Bernabéu Stadium,[2] he returned to Mexico.

In the Apertura 2004 he had a successful season with the Tiburones Rojos in which they ended up leaders, Blanco being an important factor. During this season he gained an important following at the port, which led him to come back later on.

On 2 April 2007, Blanco ventured on to Major League Soccer in the United States and signed with Chicago Fire. He was welcomed by 5,000 fans at Toyota Park as he conducted interviews with the media, signed autographs and greeted with fans.

He was later voted as a finalist for both the M.V.P. and Newcomer of the Year awards in 2007.[3] Blanco was the 2007 Sierra Mist Goal of the Year Winner which was his first season, goal came in week 20 against RSL.[4]

Blanco was the second-highest paid player in Major League Soccer, after Los Angeles Galaxy midfielder David Beckham, earning $2.7 million a year.[5] Once again finalist for the M.V.P of the year award.

On 24 July 2008 during the MLS All-Stars vs West Ham United, Blanco won the MVP of the game with one assist and one goal, a game in which he only played 46 minutes. The MLS All-stars won 3–2.

On 19 November 2008, it was announced that Santos Laguna signed Blanco on a loan to play only for the Apertura 2008 Liguilla, after the injury of their Ecuadorian striker Christian Benítez. Blanco was formally presented to the press the next day, wearing jersey number 9, and stated that he looks forward to giving Santos a back-to-back championship.[6][7][8] Blanco scored his first goal with Santos Laguna 29 November 2008. It was penalty against San Luis goalkeeper Adrian Martinez in the return game which Santos Laguna won 2–1 and 5–2 aggregate score.

Despite Blanco Bravo announced he would retire after the end of 2012, he changed his mind and played for another 6 months with Dorados. However, after the tournament ended, he did not renew his contract and was released from Dorados on June 2013.

Cuauhtémoc Blanco enrolled with Lobos BUAP for the Apertura 2013 Liga de Ascenso Season.[12] After one year with the club, he did not renewed his contract with BUAP and was released from the club at the end of the season, in which the club failed to qualify for the play-offs.

After considering retirement, 41-year-old Cuauhtémoc officially signed with Puebla F.C. for one season, making it his last effort in Liga MX as an active player. On April 21, 2015, he played his final game in the Copa MX final against C.D. Guadalajara, appearing off the bench at minute 70. Puebla F.C. went on to win the cup and send Cuauhtemoc Blanco off as a champion in the final game of his career.

Blanco has played for Mexico at three World Cups. He was part of the squad at France '98, Korea-Japan 2002 and South Africa 2010. He was also a member of the Mexico team that won the Confederations Cup in 1999 where he was the tournament's leading scorer with six goals, including the winning goal at the Estadio Azteca against Brazil in the final. He was awarded the "Silver Shoe" and "Silver Ball" for outstanding player of the tournament. Blanco holds the record along with Brazilian Ronaldinho as the highest scoring players in the Confederations Cup with nine goals, three in 1997 and six in 1999.

In the selection for the final 23-man squad for the 2006 FIFA World Cup in Germany, then Mexico national team coach Ricardo La Volpe left Blanco out of the team. While the ostensible reason given was that Blanco was frequently injured and not in good form; some people considered this to be a consequence of the previous year's constant bickering, due to on-going personal problems between coach and player.

Blanco became part of the squad that played the 2007 CONCACAF Gold Cup, scoring one penalty goal, and the 2007 Copa América, where he scored 2 goals also from penalty kicks. On 13 September 2008, he earned his 100th cap for his country in its 2–1 World Cup qualifier victory over Canada at Tuxtla Gutiérrez, coming on with only 15 seconds left in regulation time. After the match he announced his retirement from international football.[13]

Blanco announced his return to the national team in May 2009. He became a regular member of returning coach Javier Aguirre's squad, playing in all the games throughout the Hexagonal of the World Cup Qualifying. Since then, Blanco has become an important factor in Mexico's team regaining form and confidence.

On 10 October 2009, Blanco provoked the first opposition own goal and scored the second goal in a 4–1 victory over El Salvador to help Mexico clinch a spot in the 2010 World Cup. On 17 June 2010, he scored a penalty in the 78th minute of the 2–0 win against France at the World Cup finals in South Africa.[14] With this goal he became the first Mexican to score a goal in three World Cup tournaments and the third-oldest goalscorer in World Cup history.[15][16] Blanco is considered by many to be one of the greatest penalty kickers of all time. He also has a penalty-taking record; out of a total of 58 taken, he has only missed two.

Blanco played a tribute game in 2014 against Israel at the Estadio Azteca, which symbolized his official retirement from international football. Mexico went on to win the match 3–0.

Blanco himself has accepted on Mexican television and to the press that his goal celebration is an imitation of the "Archer"[18] celebration created by former Atletico de Madrid striker Kiko Narvaez. In a 2005 interview with Mexican newspaper El Universal (Mexico City), Blanco explains that while watching a Spanish league game accompanied by his teammate Germán Villa, both players agreed to celebrate their next goal by imitating the "Archer" gesture. In the end, only Blanco did it, and jokingly reprimanded Villa for not keeping his word.[19][19] However, the Chicago Fire official website claims that Blanco celebrates scoring a goal by acting like the PrehispanicTlatoani Aztec emperor Cuauhtémoc, "in order to show respect for the Mexican people, and their indigenous Amerindian heritage".[20]

Blanco remains remembered for the Cuauhtemiña (also spelled Cuauhteminha), or Blanco Trick, which he performed notably at the 1998 World Cup.[21] In the trick, when two or more opposition players are trying to take the ball from him, he traps the ball between his feet and jumps through the defenders- releasing the ball in the air and landing with it under control as he leaves the opposition players behind.[22] The trick is easy to perform but is eye-catching and has been incorporated as a special skill into the FIFA series of football video games.